Schildhaus, Hans-Ulrich

[["dc.bibliographiccitation.firstpage","3574"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Cancer Medicine"],["dc.bibliographiccitation.lastpage","3583"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Elakad, Omar"],["dc.contributor.author","Lois, Anna‐Maria"],["dc.contributor.author","Schmitz, Katja"],["dc.contributor.author","Yao, Sha"],["dc.contributor.author","Hugo, Sara"],["dc.contributor.author","Lukat, Laura"],["dc.contributor.author","Hinterthaner, Marc"],["dc.contributor.author","Danner, Bernhard C."],["dc.contributor.author","Reuter‐Jessen, Kirsten"],["dc.contributor.author","Schildhaus, Hans‐Ulrich"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","von Hammerstein‐Equord, Alexander"],["dc.date.accessioned","2021-04-14T08:26:56Z"],["dc.date.available","2021-04-14T08:26:56Z"],["dc.date.issued","2020"],["dc.description.abstract","Abstract Background Targeting fibroblast growth factor receptor 1 (FGFR1) is a potential treatment for squamous cell lung cancer (SQCLC). So far, treatment decision in clinical studies is based on gene amplification. However, only a minority of patients have shown durable response. Furthermore, former studies have revealed contrasting results regarding the impact of FGFR1 amplification and expression on patient's prognosis. Aims Here, we analyzed prevalence and correlation of FGFR1 gene amplification and protein expression in human lung cancer and their impact on overall survival. Materials \\u0026 Methods FGFR1 gene amplification and protein expression were analyzed by fluorescence in situ hybridization and immunohistochemistry (IHC) in 208 SQCLC and 45 small cell lung cancers (SCLC). Furthermore, FGFR1 protein expression was analyzed in 121 pulmonary adenocarcinomas (ACs). Amplification and expression were correlated to each other, clinicopathological characteristics, and overall survival. Results FGFR1 was amplified in 23% of SQCLC and 8% of SCLC. Amplification was correlated to males (P = .027) but not to overall survival. Specificity of immunostaining was verified by cellular CRISPR/Cas9 FGFR1 knockout. FGFR1 was strongly expressed in 9% of SQCLC, 35% of AC, and 4% of SCLC. Expression was correlated to females (P = .0187) and to the absence of lymph node metastasis in SQCLC (P = .018) with no significant correlation to overall survival. Interestingly, no significant correlation between amplification and expression was detected. Discussion FGFR1 gene amplification does not seem to correlate to protein expression. Conclusion We believe that patient selection for FGFR1 inhibitors in clinical studies should be reconsidered. Neither FGFR1 amplification nor expression influences patient's prognosis."],["dc.description.abstract","Fibroblast growh factor receptor 1 (FGFR1) is considered a potential molecular target in squamous cell lung cancer. However, prevalence of gene amplification as well as correlation to protein overexpression have to be established. Our work has evaluated prevalence and correlation of FGFR1 gene amplification and protein expression in 421 lung cancer patient samples. image"],["dc.description.sponsorship","Deutsche Krebshilfe Foundation"],["dc.description.sponsorship","Else‐Kroener‐Fresenius Foundation"],["dc.description.sponsorship","University Medical Center Goettingen"],["dc.description.sponsorship","Chinese Scholarship Council"],["dc.identifier.doi","10.1002/cam4.2994"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17450"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82118"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","2045-7634"],["dc.relation.issn","2045-7634"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Fibroblast growth factor receptor 1 gene amplification and protein expression in human lung cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","UNSP e0120079"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Schmitz, Katja"],["dc.contributor.author","Koeppen, Hartmut"],["dc.contributor.author","Binot, Elke"],["dc.contributor.author","Fassunke, Jana"],["dc.contributor.author","Kuenstlinger, Helen"],["dc.contributor.author","Ihle, Michaela Angelika"],["dc.contributor.author","Heydt, Carina"],["dc.contributor.author","Wardelmann, Eva"],["dc.contributor.author","Buettner, Reinhard"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.contributor.author","Rueschoff, Josef"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.date.accessioned","2018-11-07T09:58:38Z"],["dc.date.available","2018-11-07T09:58:38Z"],["dc.date.issued","2015"],["dc.description.abstract","Soft tissue sarcomas are a heterogeneous group of tumors with many different subtypes. In 2014 an estimated 12,020 newly diagnosed cases and 4,740 soft tissue sarcoma related deaths can be expected in the United States. Many soft tissue sarcomas are associated with poor prognosis and therapeutic options are often limited. The evolution of precision medicine has not yet fully reached the clinical treatment of sarcomas since therapeutically tractable genetic changes have not been comprehensively studied so far. We analyzed a total of 484 adult-type malignant mesenchymal tumors by MET fluorescence in situ hybridization and MET and hepatocyte growth factor immunohistochemistry. Eleven different entities were included, among them the most common and clinically relevant subtypes and tumors with specific translocations or complex genetic changes. MET protein expression was observed in 2.6% of the cases, all of which were either undifferentiated pleomorphic sarcomas or angiosarcomas, showing positivity rates of 14% and 17%, respectively. 6% of the tumors showed hepatocyte growth factor overexpression, mainly seen in undifferentiated pleomorphic sarcomas and angiosarcomas, but also in clear cell sarcomas, malignant peripheral nerve sheath tumors, leiomyosarcomas and gastrointestinal stromal tumors. MET and hepatocyte growth factor overexpression were significantly correlated and may suggest an autocrine activation in these tumors. MET FISH amplification and copy number gain were present in 4% of the tumors (15/413). Two samples, both undifferentiated pleomorphic sarcomas, fulfilled the criteria for high level amplification of MET, one undifferentiated pleomorphic sarcoma reached an intermediate level copy number gain, and 12 samples of different subtypes were categorized as low level copy number gains for MET. Our findings indicate that angiosarcomas and undifferentiated pleomorphic sarcomas rather than other frequent adult-type sarcomas should be enrolled in screening programs for clinical trials with MET inhibitors. The screening methods should include both in situ hybridization and immunohistochemistry."],["dc.description.sponsorship","German Cancer Aid (Deutsche Krebshilfe)"],["dc.identifier.doi","10.1371/journal.pone.0120079"],["dc.identifier.isi","000352475700002"],["dc.identifier.pmid","25844809"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11760"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37407"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","MET Gene Copy Number Alterations and Expression of MET and Hepatocyte Growth Factor Are Potential Biomarkers in Angiosarcomas and Undifferentiated Pleomorphic Sarcomas"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","36"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMC Clinical Pathology"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Lokka, Suvi"],["dc.contributor.author","Scheel, Andreas H."],["dc.contributor.author","Dango, Sebastian"],["dc.contributor.author","Schmitz, Katja"],["dc.contributor.author","Hesterberg, Rudolf"],["dc.contributor.author","Rüschoff, Josef"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.date.accessioned","2019-07-09T11:40:00Z"],["dc.date.available","2019-07-09T11:40:00Z"],["dc.date.issued","2014"],["dc.description.abstract","Background Liposarcoma is the most frequent soft tissue sarcoma. Well differentiated liposarcoma may progress into dedifferentiated liposarcoma with pleomorphic histology. A minority additionally features myogenic, osteo- or chondrosarcomatous heterologous differentiation. Genomic amplification of the Mouse double minute 2 homolog (MDM2) locus is characteristic for well differentiated and dedifferentiated liposarcomas. Detection of MDM2 amplification may supplement histopathology and aid to distinguish liposarcoma from other soft tissue neoplasia. Case presentation Here we present two cases of dedifferentiated liposarcoma with challenging presentation. Case 1 features a myogenic component. As the tumour infiltrated the abdominal muscles and showed immunohistochemical expression of myogenic proteins, rhabdomyosarcoma had to be ruled out. Case 2 has an osteosarcomatous component resembling extraosseous osteosarcoma. The MDM2 status was determined in both cases and helped making the correct diagnosis. Overexpression of MDM2 and co-overexpression of Cyclin-dependent kinase 4 is demonstrated by immunohistochemistry. The underlying MDM2 amplification is shown by fluorescence in situ hybridisation. Since low grade osteosarcoma may also harbour MDM2 amplification it is emphasised that the amplification has to be present in the lipomatous parts of the tumour to distinguish liposarcoma from extraosseous osteosarcoma. Conclusions The two cases exemplify challenges in the diagnoses of dedifferentiated liposarcoma. Liposarcoma often has pleomorphic histology and additionally may feature heterologous components that mimic other soft tissue neoplasms. Amplification of MDM2 is characteristic for well differentiated and dedifferentiated liposarcomas. Determination of the MDM2 status by in situ hybridisation may assist histopathology and help to rule out differential diagnoses."],["dc.identifier.doi","10.1186/1472-6890-14-36"],["dc.identifier.fs","611818"],["dc.identifier.pmid","25126005"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10586"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58073"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Challenging dedifferentiated liposarcoma identified by MDM2-amplification, a report of two cases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]